Pharmacokinetics Flashcards
A drug has a volume of distribution of 0.35 L/kg. In a 70-kg patient, what IV loading dose must be administered to achieve a plasma concentration of 8 mg/L?
196 mg
loading dose= (Vd x desired Cp)/ bioavailability
_______ describes the relationship between the administered dose of a drug and the plasma concentration that results
Volume of distribution
________ is a measure of an amount of drug in a given volume.
Concentration
When is a drug in its most concentrated form?
before we administer it
The higher the Vd, the ____________ that must be given to achieve its effect.
the higher the loading dose
A drug with a Vd that exceeds total body water(>0.6 L/kg or >42 L) is assumed to be
liphophilic
A drug with a Vd that is less than total body water is assumed to be
hydrophilic
What is the volume of distribution equation?
Vd= amount of drug/desired plasma concentration
Volume of distribution must assume two things:
the drug distributes instantaneously
the drug is not subjected to biotransformation or elimination before it fully distributes
Total body water in a 70 kg patient is
42 L
Extracellular fluid in a 70 kg patient is
14 L
Intracellular fluid in a 70 kg patient is
28 L
What patient characteristics affect volume of distribution?
pregnancy & burns
What drug characteristics affect volume of distribution?
molecular size, ionization, & protein binding
Liphophilic means that
it distributes into the total body water as well as into the fat
Liphophilic requires a ______ dose to achieve a given plasma concentration
higher
Hydrophilic means that a drug
distributes into some or all of the body water but it does not distribute into fat
What is the loading dose equation?
loading dose= Vd x (desired plasma concentration/bioavailability)
For an IV medication, bioavailability is equal to
1 since it’s injected directly into the bloodstream
The higher the volume of distribution, the __________ the loading dose that must be given to achieve the predetermined plasma concentration.
higher
How much water does the plasma volume contain?
4 L
How much water does the interstitial fluid contain in a 70 kg patient?
10 L
Clearance is directly proportional to:
a. blood flow to clearing organ
b. half-life
c. extraction ratio
d. concentration in the central compartment
A & C
Clearance is the
volume of plasma that is cleared of drug per unit time
Clearance is directly proportional to
blood flow to the clearing organ, extraction ratio, and drug dose
Clearance is inversely proportional to
half-life and drug concentration in the central compartment
To maintain a steady-state concentration in the plasma, the infusion rate or dosing interval must
equal the rate of drug clearance
As a general rule, steady-state is achieved after
five half-times
If a drug has a long half-life, you can achieve steady state faster by
administering a loading dose
The most important clearing organs include
liver, kidney, organ independent (Hofmann elimination and ester hydrolysis in the plasma)
Steady-state occurs when the
amount of drug entering the body is equivalent to the amount of drug eliminated from the body-there is a stable plasma concentration
The plasma concentration curve in a two compartment model illustrates the
biphasic decrease of a drug’s plasma concentration after a rapid IV bolus
The alpha phase of a plasma concentration curve represents
distribution from the central compartment (the plasma) to the peripheral compartment (the tissues)
The beta phase of a plasma concentration curve represents
elimination from the central compartment
A rate constant describes the
speed at which a reaction occurs (or how fast a molecule moves between compartments)
Most of the drugs we administer follow a ________ model
multi-compartment model (3 or more)
The steeper the slope of line A on a plasma concentration curve, the more _____ the drug is
liphophilic the drug is & the large the volume of distribution
The relatively flatter slope (beta phase) of the plasma concentration curve represents
drug elimination from the central compartment
Describe K12
the rate constant for drug transfer from the central to the peripheral compartment
Describe K21
the rate constant for drug transfer from the peripheral to the central compartment
Describe ke
the rate constant for drug elimination from the body
After administering an IV drug that distributes into a one-compartment model, the patient’s serum contains 6.25% of the original dose. How many half-lives have elapsed?
4
Elimination half-life is the
time it takes for 50% of the drug to be eliminated from the body after a rapid IV injection
Elimination half-time is the time
it takes for 50% of the drug to be removed from the plasma during the elimination phase
By convention, we say that a drug is cleared from the body when
96.9% of the dose has been eliminated from the plasma
The concept of context-sensitive half-time takes the
duration of drug administration into account
it’s the time required for the plasma concentration to decline by 50% after the infusion is stopped
The half-time measures a ________ and NOT a _________
constant fraction and not a constant amount
The concept of half-times is really only applicable to drugs that follow
a one-compartment model
In order of longest, what is the context sensitive half-time of the four main opioids?
fentanyl, alfentanil, sufentanil, remifentanil
What is the “context” in context-sensitive half-time?
duration of infusion (time)
Which opioid has a similar context-sensitive half-time regardless of infusion duration?
remifentanil
